The principal reason for the altered vessel structure in arteriosclerosis is the proliferation of smooth muscle cells and their production of an excessive amount of extracellular matrix including collagen, elastin, glycosaminoglycans and glyco-proteins. This response of the smooth muscle cells is thought to represent an injury reaction possibly initially of the endothelium to factors of diverse nature and origin (diet, serum lipid types and levels, hypertension, genetic predisposition, smoking habits, etc.). Platelets appear to act at several points in the injury reaction: interaction with subendothelial matrix at sites of endothelial loss to preserve vascular integrity; formation of platelet thrombi and participation in local blood clotting reactions; stimulation of smooth muscle cell proliferation; and degradation of extracellular materials by release of neutral proteases. We intend to study several of the reciprocal influences of platelets, smooth muscle and endothelial cells and the extracellular matrix in culture since we conclude that these cellular and macromolecular elements play a principal role in the genesis of the arteriosclerotic plaque. Cell cultures of endothelial and smooth muscle cells will be established from human vessels. Platelets will be exposed to purified collagens, elastin, proteoglycans and glycoproteins obtained from human aortas to elicit platelet aggregation and/or the release reaction. The factors released by the platelets will be added to the cultures of smooth muscle and endothelial cells to determine their influence on cell proliferation, cell matrix synthesis and matrix degradation. Matrix degradation will also be examined with direct platelet extracts.